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1.A.64 The Plasmolipin (Plasmolipin) Family

Plasmolipin (PLLP) is an 18-kDa proteolipid or lipoprotein found in kidney and brain, where it is restricted to the apical surface of tubular epithelial cells and to mammalian myelinated tracts, respectively. This protein is made during sciatic nerve development and regeneration in the rat. It has 182 aas and 4 TMSs (Fischer and Sapirstein, 1994). Addition of plasmolipin to lipid bilayers induces the formation of ion channels, which are voltage-dependent and K+-selective (Tosteson and Sapirstein, 1981). PLLP functions in myelin biogenesis through organization of myelin liquid-ordered membranes in the Golgi complex (Yaffe et al. 2015).

Plasmolipin has many homologues. These are referred to as CKLF-like MARVEL transmembrane domain containing protein, chemokine-like factor and T-cell differentiation marker (Mitsugumin and Synaptogyrin). Most are about 180 - 210 residues, but several are about twice as large with 8 TMSs and an internal repeat (e.g., the myeloid-associated differentiation marker of humans (MAL or MYADM; Q96S97) or the rat (EAL84950). Synthesis of these proteins is induced by retinoic acid (Cui et al., 2001). 

Plasmolipin localizes to and recycles between the plasma membrane and the Golgi complex. In the Golgi complex, it forms oligomers which block Golgi to plasma membrane transport of the secretory  vesicular stomatitis virus G protein (VSVG) (Yaffe et al. 2015). Homologues, CMTM2A and 2B, (TC# 1.A.64.5.6 and 5.7, respectively) are required for male fertility (Fujihara et al. 2018).

The transport reaction that occurs with plasmolipin in artificial membranes is:

Ions (in) Ions (out)

References associated with 1.A.64 family:

Carmosino, M., F. Rizzo, G. Procino, D. Basco, G. Valenti, B. Forbush, N. Schaeren-Wiemers, M.J. Caplan, and M. Svelto. (2010). MAL/VIP17, a New Player in the Regulation of NKCC2 in the Kidney. Mol. Biol. Cell 21: 3985-3997. 20861303
Chen, X., H. Shen, H. Liu, L. Tan, and N. Zhang. (2024). CMTM 6 promotes the development of thyroid cancer by inhibiting NIS activity through activating the MAPK signaling pathway. Funct Integr Genomics 24: 10. 38221563
Cui W., L. Yu, H. He, Y. Chu, J. Gao, B. Wan, L. Tang, S. Zhao. (2001). Cloning of human myeloid-associated differentiation marker (MYADM) gene whose expression was up-regulated in NB4 cells induced by all-trans retinoic acid. Mol Biol Rep. 28(3): 123-138.
Fischer I. and V.S. Sapirstein. (1994). Molecular cloning of plasmolipin. Characterization of a novel proteolipid restricted to brain and kidney. J. Biol. Chem. 269: 24912-24919. 7929173
Fujihara, Y., A. Oji, K. Kojima-Kita, T. Larasati, and M. Ikawa. (2018). Co-expression of sperm membrane proteins CMTM2A and CMTM2B is essential for ADAM3 localization and male fertility in mice. J Cell Sci 131:. 30209135
Hartzell, H.C., Z. Qu, K. Yu, Q. Xiao, and L.T. Chien. (2008). Molecular physiology of bestrophins: multifunctional membrane proteins linked to best disease and other retinopathies. Physiol. Rev. 88: 639-672. 18391176
Li, D., C. Jin, C. Yin, Y. Zhang, B. Pang, L. Tian, W. Han, D. Ma, and Y. Wang. (2007). An alternative splice form of CMTM8 induces apoptosis. Int J Biochem. Cell Biol. 39: 2107-2119. 17681841
Mezzadra, R., C. Sun, L.T. Jae, R. Gomez-Eerland, E. de Vries, W. Wu, M.E.W. Logtenberg, M. Slagter, E.A. Rozeman, I. Hofland, A. Broeks, H.M. Horlings, L.F.A. Wessels, C.U. Blank, Y. Xiao, A.J.R. Heck, J. Borst, T.R. Brummelkamp, and T.N.M. Schumacher. (2017). Identification of CMTM6 and CMTM4 as PD-L1 protein regulators. Nature 549: 106-110. 28813410
Miyazaki, A., S. Yogosawa, A. Murakami, and D. Kitamura. (2012). Identification of CMTM7 as a transmembrane linker of BLNK and the B-cell receptor. PLoS One 7: e31829. 22363743
Rubio-Ramos, A., L. Labat-de-Hoz, I. Correas, and M.A. Alonso. (2021). The MAL Protein, an Integral Component of Specialized Membranes, in Normal Cells and Cancer. Cells 10:. 33946345
Steed, E., N.T. Rodrigues, M.S. Balda, and K. Matter. (2009). Identification of MarvelD3 as a tight junction-associated transmembrane protein of the occludin family. BMC Cell Biol 10: 95. 20028514
Tosteson, M.T. and V.S. Sapirstein. (1981). Protein interactions with lipid bilayers: the channels of kidney plasma membrane proteolipids. J. Membr. Biol. 63: 77-84. 6273572
Yaffe, Y., I. Hugger, I.N. Yassaf, J. Shepshelovitch, E.H. Sklan, Y. Elkabetz, A. Yeheskel, M. Pasmanik-Chor, C. Benzing, A. Macmillan, K. Gaus, Y. Eshed-Eisenbach, E. Peles, and K. Hirschberg. (2015). The myelin proteolipid plasmolipin forms oligomers and induces liquid-ordered membranes in the Golgi complex. J Cell Sci 128: 2293-2302. 26002055
Zhou, J., J. Lei, J. Wang, C.L. Lian, L. Hua, Z.Y. He, and S.G. Wu. (2019). Bioinformatics-Based Discovery of -Like Transmembrane Member 5 as a Novel Biomarker for Breast Cancer. Front Cell Dev Biol 7: 361. 31998718